7. PROJECT SUMMARY Background: An emerging epidemic of hepatitis C virus (HCV) infection exists among young persons who inject drugs (PWID) from suburban and rural areas. HCV is primarily transmitted via risk practices associated with injection drug use (IDU). In 2016, the National Academy of Sciences (NAS) examined the feasibility of HCV elimination in the U.S., defined as cessation of viral transmission in this country. In its phase-1 report, NAS determined that young PWID are the people at greatest risk for HCV and are the primary drivers of HCV incidence today in non-urban U.S. communities that previously had low to modest rates of HCV infection. To date, no known study has fully elucidated why HCV incidence is increasing in this ?new generation? of PWID (NG-PWID), which is composed predominantly of non-Hispanic Whites from suburban and rural communities. Our recent study suggests that what may have changed over the past decade are contextual and structural factors that heighten suburban NG-PWID's risk of becoming HCV-infected. Objective: We propose a longitudinal study among NG-PWID and their personal (egocentric) injection, sexual, and support networks. We will collect data every 6 months for 36 months to assess over time the impact on HCV risk of (i) social network factors, (ii) physical and social geographic factors, (iii) social norms of IDU, and (iv) perceived IDU and HCV stigma. Methods: We will recruit 420 PWID (ages 18-30) and about 1,156 of their injection network members (age 18 and over) from Chicago, Illinois, and surrounding suburban areas. Recruitment will occur at two community field sites of a large syringe services program (SSP) and through direct outreach in large, open drug market areas. Six types of data will be collected on both participants and their injection, sexual, and support network members: (i) participant socio-demographic characteristics, drug use patterns and practices, and sexual practices, (ii) network size, characteristics, and features of relationships among network members (e.g., strength of tie), (iii) HIV and HCV infection status through testing, (iv) geographic data on the location and characteristics of places where participants and their network members reside, purchase drugs, inject, and meet sex and injection partners, (v) an assessment of social norms within both the participant's network and specific behavioral settings, and (vi) an assessment of perceived IDU and HCV stigma. Public Health Significance: The proposed research will (i) improve our understanding of the contextual and structural factors driving HCV incidence among NG-PWID, (ii) inform the development of innovative strategies for NG-PWID (e.g., network interventions, direct antiviral HCV treatment scale up) toward the goal of HCV elimination in the U.S. set forth by DHHS, and (iii) provide crucial data needed to develop more realistic computational models that address the complex interplay of individual, social, and structural level factors affecting HCV incidence in order to identify the most effective combination(s) of intervention strategies for achieving HCV elimination.